Norman Sussman, MD - Ogden Surgical
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Transcript Norman Sussman, MD - Ogden Surgical
OGDEN SURGICAL-MEDICAL SOCIETY
68TH ANNUAL CONFERENCE - 2013
What the LFTs are Telling You
Avoiding Common Mistakes
Norman L. Sussman, MD
Baylor College of Medicine
Houston, Texas
S
OGDEN SURGICAL-MEDICAL SOCIETY
68TH ANNUAL CONFERENCE - 2013
This presentation has no commercial content,
promotes no commercial vendor and is not
supported financially by any commercial
vendor.
I receive no financial remuneration from any
commercial vendor related to this presentation
Question 1: Acute or Chronic?
Cirrhosis
Platelets
Imaging
Chronicity & severity
Prior studies
Albumin
Bilirubin
INR
Injury
ALT/AST
Cholestasis
Alk Phos
GGT
5’NT
Biliary imaging
U/S, MRCP, ERCP
Question 2: Hepatocellular or Cholestatic
ALT/ULN
AP/ULN
>5 = hepatocellular
<2 = cholestatic
Or, just look at the fold increase of ALT and AP
Normal ALT
Women < 19 IU/mL
Men < 30 IU/mL
Aspartate Aminotransferase (AST/SGOT)
Alanine Aminotransferase (ALT/SGPT)
Markers of Cell Destruction
ALT is more specific to the liver
Usually higher in chronic liver injury (steady state)
Viral hepatitis, AIH, NAFLD
AST may be higher than ALT
Cirrhosis
Alcohol (pyridoxine deficiency)
Early phase of acute liver injury
Other organ damage – eg rhabdomyolysis, tumors
Acute Liver injury
Acetaminophen, Shock, IV Amiodarone
Dynamic AST/ALT Ratio
Peak injury about 48 hrs
AST is initially 2x ALT
Differential clearance
AST – 50%/day
ALT – 33%/day
Equalize at about 96 hrs
Bilirubin, INR, and
creatinine are key to
assessing survival
Remien et al., Hepatology 2012
MALD
Model of Acetaminophen-related Liver Damage
Remien et al., Hepatology 2012
Biliary Architecture - Bile Flow
Epithelial Cells are Polarized
Hollow Organ
Liver
Lumen = Bile Canaliculus = Brush Border
Basolateral Aspect
Alkaline Phosphatase
Located on the bile canliculus
Phospholipase C
Three genes
cleavage site
Liver/kidney/bone
Intestine
Placenta (man and great apes)
PI-glycan anchor (PI-g tailed proteins)
GGT, 5’-nucleotidase
GGT is inducible by alcohol
Access to the sinusoid (blood side of the cell)
Low in patients with Wilson disease
Albumin & AFP
Proteins – made by the liver
AFP is the fetal analogue of albumin
Made when cells revert to a fetal phenotype
– part of a coordinated switch to fetal genes
Liver regeneration (eg recovery from ALF)
Inflammation (injury with regeneration)
Liver cancer
Prealbumin
Actually Transthyretin
Transports thyroxine and retinol
Used to assess nutrition
2-4 day half life
Affected by inflammation
Mis-folded TTR is the most common protein
in amyloid
Bilirubin Transport
Bilirubin
Organic anion derived from hemoglobin
Measured by diazo (Van Den Bergh) reaction
Direct (conjugated) vs. indirect
Indirect – albumin-bound
Direct – water soluble (urine)
Delta (albumin-bound) – clears slowly
Liver disease conjugated bilirubinemia
Jaundice may occur in right heart failure
Y = sufate,
glucuronate
Z = glycine,
taurine
NTCP – Na
Taurocholate
Cotransporting
Polypeptide
MRP2 –
Multidrug
Resistance
Protein 2
BSEP –
Bile Salt
Export
Protein
OATP –
Organic
Anion
Transport
Protein
Canalicular Transporters & Diseases
Unknown
Bile acids
Sterols
Phospholipids
Conjugated Bilirubin
& other conjugates
FIC1 – PFIC1
BSEP – PFIC2
ABC G5/G8 – Sitosterolemia
MDR3 – PFIC3
MRP2 – Dubin-Johnson
Coagulation Factors
Liver makes factors I, II, V, VII, IX, X
PT/INR: I, II, V, VII, X
Prolonged PT/INR:
Congenital
Liver failure
Vitamin K deficiency
Warfarin
Vitamin K dependent factors: II, VII, IX, X
FV – shortest half-life and not vitamin K dep.
Vitamin K replacement
Ammonia
Not especially useful
Occasional adult with urea cycle defect
MELD Formula
The Basis for Organ Allocation since Feb 2002
6.3 + ([0.957 x log creat] + [0.378 x log bili] +
[1.12 x log INR] + 0.643) x 10
Score
<10
10-19
20-29
30-39
>40
90 Day Mortality (%)
2-8
6-29
50-76
62-83
100
The 2g Sodium Diet
Spot urine Na+>K+ predicts >78 mmol sodium
excretion with 90% accuracy
2g Na+ = 88 mmole
78 mmol urinary + 10 mmol involuntary loss
Patients who excrete >78 mmol/24h can be treated
with 2g dietary restriction alone
Assess excretion with 24h urinary sodium
24h creatinine excretion to test completeness
15 mg/kg for men) or 10 mg/kg for women
If spot urine Na+>K+, the patient is excreting >78
mmol Na+ (i.e. consuming >2 Na+ per day)
Hyponatremia
997 consecutive patients from 28 centers in Europe, North
and South America, and Asia for 28 days
Inpatients and outpatients with cirrhosis and ascites
Serum Sodium
(mEq/L)
Heptorenal Syndrome
Hepatic Encephalopathy
GI bleeding
Bacterial Peritonitis
<130
131-135
>135
3.45
3.40
1.48
2.36
1.75
1.69
0.93
1.44
1 (ref)
1 (ref)
1 (ref)
1 (ref)
Angeli P et al. Hepatology. 2006;44:1535–1542.
Hyponatremia – MELD-Na
Kim et al, NEJM
2008;359:1018-26
Liver Failure
Liver injury
ALT & AST
Synthetic failure
INR, F-V, F-VII
Albumin
Bilirubin
Portal hypertension
Ascites/edema
Encephalopathy
Varices
Renal failure
Cardiomyopathy
Pulmonary Disease
Viral Hepatitis
Acute hepatitis panel
Anti-HAV IgM, anti-HBc IgM, HBsAg, anti-HCV
The rest
HAV immunity: anti-HAV (total)
Anti-HBc (total), anti- HBs
Viral titers: HBV DNA, HCV RNA
Hepatitis B
Anti-HBc
IgM – current infection or flare
IgG – prior infection
HBsAg: current infection
Anti-HBs: immunity (titer)
HBeAg and anti-HBe: stage of disease
Autoimmune Markers
AIH
Usual: ANA, ASMA, anti-actin, LKM
Unusual: SLA, ASGP, ANCA
Increased IgG
PBC
AMA
Increased IgM
PSC: None
IgG4
Gender
Female
+2
HLA
AP:AST (or ALT)
ratio
>3
<1.5
-2
+2
-globulin or IgG
above normal
>2.0
1.5-2.0
1.0-1.5
<1.0
ANA, SMA, or antiLKM1 titers
>1:80
1:80
1:40
<1:40
DR3 or DR4
+1
Immune disease
Thyroiditis, colitis,
others
+2
+3
+2
+1
0
Other markers
Anti-SLA, actin,
LC1, pANCA
+2
+3
+2
+1
0
Histological features
Interface hepatitis
Plasmacytic
Rosettes
None of above
Biliary changes
Other features
+3
+1
+1
-5
-3
-3
Treatment response
Complete
Relapse
+2
+3
AMA
Positive
-4
Viral markers
Positive
Negative
-3
+3
Yes
No
-4
+1
Pretreatment score:
Definite diagnosis
Probable diagnosis
<25 g/day
>60 g/day
+2
-2
Post-treatment score:
Drugs
Alcohol
Definite diagnosis
Probable diagnosis
>15
10-15
>17
12-17
*Adapted from Alvarez F, Berg PA, Bianchi FB, et al. J. Hepatology 1999;31:929-938.
AMA-Positive & AMA-Negative PBC
Autoantibody
AMA+ Group (%)
AMA- Group (%)
AMA
100
0
ANA
20-15
71-100
gp210
10-20
50
p63
25
25
Laminin B receptor
<1
<1
20-30
30-40
Promyelocytic leukemia protein
22
?
sp140
10
53
10-15
?
Centromere
<5
?
Laminin B
22
14-41
26-49
29
sp100
SOX13
SMA
Vierling JM. Clin Liver Dis. 2004; 8:177-94
FibroTest/Fibrosure®
Five serum tests
a-2 macroglbulin
Haptoglobin
GGT
T-bilirubin
Apolipoprotein A1
For a cutoff of 0.31, the negative predictive
value for excluding significant fibrosis = 91%
49 year old female
Admitted through the
ER with jaundice, fever,
chills, and RUQ pain for
past three days
Pain worse when the car
hit a bump
U/S: thickened gall
bladder, large liver
Murphy sign during u/s
ALT
AST
AP
Bili/D
Alb
INR
WBC
Hb
Plate
18
36
180
12.4/10.9
3.1
2.3
18.7
11.4
98,0000
Does this patient need a cholecystectomy?
History
Gallstones – mother and grandmother
Works from home
Drinks – 1-2 glasses of Scotch daily
Diagnosis – acute alcoholic hepatitis
Summary
ALT/AST = liver injury
ALT is higher in hepatitis
AST his higher in acute liver injury and
cirrhosis
AP/GGT/5’NT = cholestasis
Wilson disease = low AP
AFP is an analogue of albumin = regeneration
Summary
Bilirubin
Direct = cholestasis & liver injury
Indirect = hemolysis, Gilbert
Serum ammonia has little utility
Occasional urea cycle defect
PT/INR – higher in zone 3 necrosis
Severe liver injury
Hyperbilirubinemia
Abnormal clotting